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Acceso Abierto Actividad antimicrobiana de germicidas halogenados frente a aislamientos hospitalarios(2001) Magariños, María del Carmen; Penacca, Alejandra C.; Castelo, Sandra M.; Martínez, Anabela M.; Demartini, Eduardo A.; Landriel, Lorena; Reynaldo, Mirta BeatrizAntiseptics and disinfectants are extensively used in hospitals and health care settings for a variety of topical and hard-surface applications. In particular, they are essential part of infection control practices and in the prevention of nosocomial infections. Despite this, few is known about the mode of action of these biocides with respect to antibiotics. In general, the antimicrobial activity can be influenced by many factors such as formulation effects, presence of organic matter, synergy, temperature, dilution and test method. The widespread use of antiseptics and disinfectant products has prompted some speculation on the development of microbial resistance, in particular cross-resistance to antibiotics. The aim of this study was to evaluate microbiological resistance to halogenated compounds by studying the behaviour of the grampositive and gramnegative clinical isolates against halogenated biocides usually applied, with and without organic substance and applying distilled water, potable water and water of 300 ppm hardness as dilution means. The results indicate that the hospital microorganisms show a higher resistance to the biocides than the strain Staphylococcus aureus ATCC 6538, although the effective concentration in clean conditions was lesser than the recommended ones, for all the dilution means. In presence of organic matter the antimicrobial activity was reduced in accordance with the bactericidal concentration of each microorganisrn, due to the oxidant action of these disinfectants - Artículo
Acceso Abierto Is Oreochromis niloticus invading the Samborombón Bay, Río de la Plata, Argentina?(Museo Argentino de Ciencias Naturales "B. Rivadavia" (MACN), 2010) García, Mirta L.; Cuello, Mariela; Solari, Agustín; Milessi, Andres Conrado; Cortés, Federico; Bruno, Ignacio M.; Zapata, María F.The Nile tilapia (Oreochromis niloticus) is a species widely cultivated worldwide. In recent decades it was an increasing development of fish farming of this species and the red variety in Argentina and Uruguay. From January to March 2010, four specimens of O. niloticus were captured in the south boundary of Samborombón Bay (S 36° 17´- W 56° 46´), which is the external sector of the Río de la Plata. Probably the collected specimens were released accidentally from hatcheries placed on the banks of aquatic environments in communication with the Samborombón Bay. The patterns and mechanisms of species dispersal are of significant interest, while the interactions among factors determining invasion success often remain poorly understood. Invasion success is influenced by the ability of invading specie to withstand, interactions with native species and oceanographic characteristics of the new habitat. Of four specimens obtained two were females, one in spawning stage. This is the first record of Nile tilapia from a natural environment in Argentina and could indicate the beginning of a new invasion by a non native species. - Artículo
Acceso Abierto Oral Metformin Treatment Prevents Enhanced Insulin Demand and Placental Dysfunction in the Pregnant Rat Fed a Fructose-Rich Diet(Hindawi Publishing Corporation, 2012) Alzamendi, Ana; Del Zotto, Héctor; Castrogiovanni, Daniel; Romero, José; Giovambattista, Andrés; Spinedi, EduardoThe intake of a fructose-rich diet (FRD) in the normal female rat induces features similar to those observed in the human metabolic syndrome phenotype. We studied the impact of FRD administration to mothers on pregnancy outcome. On gestational day (Gd) zero rats were assigned to either group: ad libitum drinking tap water alone (normal diet, ND) or containing fructose (10% w/vol; FRD) through pregnancy; all rats were fed a Purina chow diet ad libitum ND and FRD rats were daily cotreated or not with metformin (60 mg/Kg/day oral; ND + MF and FRD + MF) and submitted to a high glucose load test on Gd 14. Additionally, placentas from different groups were studied on Gd 20. Data indicated that: (1) although FRD rats well tolerated glucose overload, their circulating levels of insulin were significantly higher than in ND rats; (2) the mesometrial triangle blood vessel area was significantly lower in placentas from FRD than ND dams; (3) the detrimental effects of FRD administration to mothers were ameliorated by metformin cotreatment. Our study suggests that excessive intake of fructose during pregnancy enhanced the risk for developing gestational diabetes and subsequent preeclampsia, and that metformin prevented the poor pregnancy outcome induced by FRD. - Artículo
Acceso Abierto Effect of Pioglitazone on the Fructose-Induced Abdominal Adipose Tissue Dysfunction(Hindawi Publishing Corporation, 2012) Alzamendi, Ana; Giovambattista, Andrés; Garcia, María Elisa; Rebolledo, Oscar R.; Gagliardino, Juan José; Spinedi, EduardoAim. To test the potential role of PPARγ in the endocrine abdominal tissue dysfunction induced by feeding normal rats with a fructose rich diet (FRD) during three weeks. Methodology. Adult normal male rats received a standard commercial diet (CD) or FRD, (10% in drinking water) without or with pioglitazone (PIO) (i.p. 0.25mg/Kg BW/day; CD-PIO and FRD-PIO). Thereafter, we measured circulating metabolic, endocrine, and oxidative stress (OS) markers, abdominal adipose tissue (AAT) mass, leptin (LEP) and plasminogen activator inhibitor-1 (PAI-1) tissue content/expression, and leptin release by isolated adipocytes incubated with different concentrations of insulin. Results. Plasma glucose, insulin, triglyceride, TBARS, LEP, and PAI-1 levels were higher in FRD rats; PIO coadministration fully prevented all these increments. AAT adipocytes from FRD rats were larger, secreted a higher amount of LEP, and displayed decreased sensitivity to insulin stimulation; these effects were significantly ameliorated by PIO. Whereas AAT LEP and PAI-1 (mRNA) concentrations increased significantly in FRD rats, those of insulin-receptor-substrate- (IRS-) 1 and IRS-2 were reduced. PIO coadministration prevented FRD effects on LEP, PAI-1, and IRS-2 (fully) and IRS-1 (partially) mRNAs in AAT. Conclusion. PPARγ would play a relevant role in the development of the FRD-induced metabolicendocrine dysfunction. - Artículo
Acceso Abierto Ghrelin Indirectly Activates Hypophysiotropic CRF Neurons in Rodents(2012) Cabral, Agustina; Suescun, Olga; Zigman , J.M.; Perelló, MarioGhrelin is a stomach-derived hormone that regulates food intake and neuroendocrine function by acting on its receptor, GHSR (Growth Hormone Secretagogue Receptor). Recent evidence indicates that a key function of ghrelin is to signal stress to the brain. It has been suggested that one of the potential stress-related ghrelin targets is the CRF (Corticotropin-Releasing Factor)-producing neurons of the hypothalamic paraventricular nucleus, which secrete the CRF neuropeptide into the median eminence and activate the hypothalamic-pituitary-adrenal axis. However, the neural circuits that mediate the ghrelin-induced activation of this neuroendocrine axis are mostly uncharacterized. In the current study, we characterized in vivo the mechanism by which ghrelin activates the hypophysiotropic CRF neurons in mice. We found that peripheral or intra-cerebro-ventricular administration of ghrelin strongly activates c-fos – a marker of cellular activation – in CRFproducing neurons. Also, ghrelin activates CRF gene expression in the paraventricular nucleus of the hypothalamus and the hypothalamic-pituitary-adrenal axis at peripheral level. Ghrelin administration directly into the paraventricular nucleus of the hypothalamus also induces c-fos within the CRF-producing neurons and the hypothalamic-pituitary-adrenal axis, without any significant effect on the food intake. Interestingly, dual-label immunohistochemical analysis and ghrelin binding studies failed to show GHSR expression in CRF neurons. Thus, we conclude that ghrelin activates hypophysiotropic CRF neurons, albeit indirectly. - Artículo
Acceso Abierto Fructose Rich Diet-Induced High Plasminogen Activator Inhibitor-1 (PAI-1) Production in the Adult Female Rat: Protective Effect of Progesterone(MDPI (Multidisciplinary Digital Publishing Institute), 2012) Castrogiovanni, Daniel; Alzamendi, Ana; Ongaro, Luisina; Giovambattista, Andrés; Gaillard, Rolf; Spinedi, EduardoThe effect of progesterone (P4) on fructose rich diet (FRD) intake-induced metabolic, endocrine and parametrial adipose tissue (PMAT) dysfunctions was studied in the adult female rat. Sixty day-old rats were i.m. treated with oil alone (control, CT) or containing P4 (12 mg/kg). Rats ate Purina chow-diet ad libitum throughout the entire experiment and, between 100 and 120 days of age drank ad libitum tap water alone (normal diet; CT-ND and P4-ND) or containing fructose (10% w/v; CT-FRD and P4-FRD). At age 120 days, animals were subjected to a glucose tolerance test or decapitated. Plasma concentrations of various biomarkers and PMAT gene abundance were monitored. P4-ND (vs. CT-ND) rats showed elevated circulating levels of lipids. CT-FRD rats displayed high (vs. CT-ND) plasma concentrations of lipids, leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). Lipidemia and adiponectinemia were high (vs. P4-ND) in P4-FRD rats. Although P4 failed to prevent FRD-induced hyperleptinemia, it was fully protective on FRD-enhanced plasma PAI-1 levels. PMAT leptin and adiponectin mRNAs were high in CT-FRD and P4-FRD rats. While FRD enhanced PMAT PAI-1 mRNA abundance in CT rats, this effect was absent in P4 rats. Our study supports that a preceding P4-enriched milieu prevented the enhanced prothrombotic risk induced by FRD-elicited high PAI-1 production. - Artículo
Acceso Abierto Determinantes sociales adversos y riesgo para anomalías congénitas seleccionadas(Sociedad Argentina de Pediatría (SAP), 2014) Pawluk, Mariela S.; Campaña, Hebe Edith; Gili, Juan; Comas, Belén; Giménez, Lucas; Villalba, María I.; Scala, Sandra C.; Poletta, Fernando A.; López Camelo, Jorge SantiagoIntroducción. Diferentes trabajos han relacionando condiciones sociales adversas a nivel familiar y regional con resultados perinatales (mortalidad neonatal, bajo peso y prematuridad); sin embargo, pocos estudiaron el efecto de la pobreza sobre anomalías congénitas. Objetivo. Evaluar el riesgo de ocurrencia de 25 anomalías congénitas y determinantes sociales adversos según el nivel socioeconómico de la familia y de la región. Población y métodos. Estudio caso-control exploratorio, en el que se utilizaron datos del Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). La muestra consistió en 3786 recién nacidos vivos con una única malformación y 13 344 controles, seleccionados entre 546 129 nacimientos, ocurridos en 39 hospitales de Argentina durante el período 1992-2001. Se estimaron los riesgos (OR) directos, indirectos (a través de la región de residencia) y la interacción entre el nivel socioeconómico individual y residencial para cada uno de los 25 defectos congénitos. Resultados. Los defectos labio leporino con/sin paladar hendido (OR= 1,43) y comunicación interventricular (OR= 1,38) mostraron un riesgo significativamente mayor en el nivel socioeconómico más bajo. Los niveles socioeconómicos bajos se asociaron de manera significativa con una mayor frecuencia de consanguinidad parental, ancestros nativos, edad materna menor de 19 años, más de 4 embarazos, bajo número de visitas prenatales y residencia en regiones desfavorables. Conclusión. La fisura labial con o sin paladar hendido y los defectos del tabique interventricular estuvieron asociados significativamente con un nivel socioeconómico más bajo. La falta de planificación familiar, de control prenatal y la exposición a agentes ambientales o teratógenos pueden explicar estos hallazgos. - Artículo
Acceso Abierto Linajes paternos del Gran Chaco, un abordaje desde el ADN(2014) Jurado Medina, Laura Smeldy; Ramallo, Virginia; Calandra, Horacio; Lamenza, Guillermo; Braunstein, José; Salceda, Susana; Bailliet, GracielaLa región no recombinante del cromosoma Y ha sido exitosamente utilizada para reconocer la estructura genética de los linajes paternos de poblaciones humanas. Este trabajo se integra al proyecto multidisciplinario “De las historias étnicas a la prehistoria en el Gran Chaco”, involucra el estudio de individuos de diversa filiación étnica y se propone reconocer la estructuración en la fracción nativa de los linajes paternos. Tal información dará cuenta de la dinámica poblacional y de los patrones de distribución aportando así, elementos clarificadores de la compleja configuración de las poblaciones chaqueñas. En los 118 individuos analizados se identificaron 82 linajes, de los cuales 22% estuvieron presentes en más de un individuo dentro de una población o entre poblaciones, en ocasiones distantes geográficamente. El coeficiente de diferenciación entre poblaciones fue el mayor encontrado (FST = 21%) en linajes autóctonos de poblaciones de Argentina (FST = 3%). La red de haplotipos demuestra que los linajes presentan una subestructuración en 3 ramas principales, en cada una de las mismas participan linajes de distintos grupos, reflejando la ausencia de aislamiento entre los mismos y planteando interesantes interrogantes a la luz de los datos arqueológicos y etnolingüísticos. - Artículo
Acceso Abierto Ghrelin's orexigenic effect is modulated via a serotonin 2C receptor interaction(American Chemical Society, 2015) Schellekens, Harriet; De Francesco, Pablo; Kandil, Dalia; Theeuwes,Wessel F.; McCarthy, Triona; van Oeffelen,Wesley E.P.A.; Perelló, Mario; Giblin, Linda; Dinan, Timothy G.; Cryan, John F.Understanding the intricate pathways modulating appetite and subsequent food intake is of particular importance considering the rise in obesity incidence across the globe. The serotonergic system, specifically the 5-HT2C receptor, has shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor wellknown for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signalling is not due to coupling to GαS, as no increase in cAMP signalling is observed. Next, flowcytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate co-localized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic- and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signalling is blocked, ghrelin’s orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into biological significant modulation of ghrelin’s orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management. - Artículo
Acceso Abierto Escalation in high fat intake in a binge eating model differentially engages dopamine neurons of the ventral tegmental area and requires ghrelin signaling(2015) Valdivia Torres, Lesly Spring; Cornejo, María P.; Reynaldo, Mirta Beatriz; De Francesco, Pablo; Perelló, MarioBinge eating is a behavior observed in a variety of human eating disorders. Ad libitum fed rodents daily and time-limited exposed to a high-fat diet (HFD) display robust binge eating events that gradually escalate over the initial accesses. Intake escalation is proposed to be part of the transition from a controlled to a compulsive or loss of control behavior. Here, we used a combination of behavioral and neuroanatomical studies in mice daily and time-limited exposed to HFD to determine the neuronal brain targets that are activated – as indicated by the marker of cellular activation c-Fos – under these circumstances. Also, we used pharmacologically or genetically manipulated mice to study the role of orexin or ghrelin signaling, respectively, in the modulation of this behavior. We found that four daily and time-limited accesses to HFD induce: (i) a robust hyperphagia with an escalating profile, (ii) an activation of different sub-populations of the ventral tegmental area dopamine neurons and accumbens neurons that is, in general, more pronounced than the activation observed after a single HFD consumption event, and (iii) an activation of the hypothalamic orexin neurons, although orexin signaling blockage fails to affect escalation of HFD intake. In addition, we found that ghrelin receptor-deficient mice fail to both escalate the HFD consumption over the successive days of exposure and fully induce activation of the mesolimbic pathway in response to HFD consumption. Current data suggest that the escalation in high fat intake during repeated accesses differentially engages dopamine neurons of the ventral tegmental area and requires ghrelin signaling. - Artículo
Acceso Abierto X-ray structure of the mature ectodomain of phogrin(2015) Noguera, M.E.; Primo, María Evangelina; Jakoncic, J.; Solimena, M.; Poskus, E.; Ermácora, MarioPhogrin/IA-2β and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet β-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and β-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure-function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-Å resolution, respectively. Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel β-strands packed against two α-helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes. - Artículo
Acceso Abierto Stability and targeting of proICA512/IA-2 to insulin secretory granules requires beta4-sheet mediated dimerization of its ectodomain in the endoplasmic reticulum(2015) Torkko, J.; Primo, M.; Dirkx, R.; Friedrich, A.; Viehrig, A.; Vergari, E.; Borgonovo, B.; Sonmez, A.; Wegbrod, C.; Lachnit, M.; Munster, C.; Sica, Mauricio; Emárcora, M.; Solimena, M.The type 1 diabetes autoantigen ICA512/IA-2/RPTPN is a receptor protein tyrosine phosphatase of the insulin secretory granules (SGs) which regulates the size of granule stores, possibly via cleavage/signaling of its cytosolic tail. The role of its extracellular region remains unknown. Structural studies indicated that β2- or β4-strands in the mature ectodomain (ME ICA512) form dimers in vitro. Here we show that ME ICA512 prompts proICA512 dimerization in the endoplasmic reticulum. Perturbation of ME ICA512 β2-strand N-glycosylation upon S508A replacement allows for proICA512 dimerization, O-glycosylation, targeting to granules, and conversion, which are instead precluded upon G553D replacement in the ME ICA512 β4-strand. S508A/G553D and N506A/G553D double mutants dimerize but remain in the endoplasmic reticulum. Removal of the N-terminal fragment (ICA512-NTF) preceding ME ICA512 allows an ICA512-ΔNTF G553D mutant to exit the endoplasmic reticulum, and ICA512-ΔNTF is constitutively delivered to the cell surface. The signal for SG sorting is located within the NTF RESP18 homology domain (RESP18-HD), whereas soluble NTF is retained in the endoplasmic reticulum. Hence, we propose that the ME ICA512 β2-strand fosters proICA512 dimerization until NTF prevents N506 glycosylation. Removal of this constraint allows for proICA512 β4-strand-induced dimerization, exit from the endoplasmic reticulum, O-glycosylation, and RESP18-HD-mediated targeting to granules. - Artículo
Acceso Abierto Fasting enhances pyroglutamyl peptidase II activity in tanycytes of the mediobasal hypothalamus of male adult rats(2015) Lazcano, I.; Cabral, Agustina; Uribe, R.; Jaimes-Hoy, L.; Perelló, Mario; Joseph-Bravo, P.; Sánchez-Jaramillo, E.; Charli, J.L.Fasting down-regulates the hypothalamus-pituitary-thyroid (HPT) axis activity through a reduction of TRH synthesis in neurons of the parvocellular paraventricular nucleus of the hypothalamus (PVN). These TRH neurons project to the median eminence (ME), where TRH terminals are close to the cytoplasmic extensions of β2 tanycytes. Tanycytes express pyroglutamyl peptidase II (PPII), the TRH-degrading ectoenzyme that controls the amount of TRH that reaches the anterior pituitary. We tested the hypothesis that regulation of ME PPII activity is another mechanism by which fasting affects the activity of the HPT axis. Semiquantitative in situ hybridization histochemistry data indicated that PPII and deiodinase 2 mRNA levels increased in tanycytes after 48 hours of fasting. This increase was transitory, followed by an increase of PPII activity in the ME, and a partial reversion of the reduction in PVN pro-TRH mRNA levels and the number of TRH neurons detected by immunohistochemistry. In fed animals, adrenalectomy and corticosterone treatment did not change ME PPII activity 72 hours later. Methimazole-induced hypothyroidism produced a profound drop in tanycytes PPII mRNA levels, which was reverted by 3 days of treatment with T4. The activity of thyroliberinase, the serum isoform of PPII, was increased at most fasting time points studied. We conclude that delayed increases in both the ME PPII as well as the thyroliberinase activities in fasted male rats may facilitate the maintenance of the deep down-regulation of the HPT axis function, despite a partial reactivation of TRH expression in the PVN. - Artículo
Acceso Abierto Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats(2015) Castrogiovanni, Daniel; Ongaro, Luisina; Zuburía, Guillermina; Giovambattista, Andrés; Spinedi, EduardoRats neonatally treated withmonosodiumL-glutamate (MSG) are deeply dysfunctional in adulthood. We explored the effect of an oral low dose of metformin treatment in male MSG rats on adipoinsular axis and visceral adipose tissue (VAT) dysfunctions, in both basal (nonfasting) and endotoxemia conditions. MSG rats, treated or not treated with metformin (30 days prior to experimentation), and control litter-mates (CTR) were studied at 90 days of age. Peripheral concentrations of glucose, lipids, and hormones were determined in basal and post-lipopolysaccharide (LPS) treatment conditions. Food intake and body weight (BW) were recorded and VAT mass and leptin mRNA levels were evaluated. Data indicated that MSG rats were lighter and displayed hypercorticosteronemia, hypophagia, adipoinsular axis hyperactivity, and enhanced VAT mass associated with an increased leptin gene expression. Interestingly,metformin-treatedMSG rats corrected BWcatch-up and counteracted VAT (mass and leptinmRNA level) and adipoinsular axis (basal and post-LPS) dysfunctions. Thus metformin treatment in MSG rats is able to correct several VAT and metabolic-endocrine dysfunctions. Our study suggests that a low-dose metformin therapy is effective to correct, at least in part, adipoinsular axis dysfunction in hypertrophic obese phenotypes, such as that of the human Cushing syndrome. - Parte de libro
Embargado Genetic drift among native people from South American Gran Chaco affects interleukin 1 receptor antagonist variation(2015) Catanesi, Cecilia Inés; Glesmann, L.; Richardson, J.Genetic variation is generally responsible for ethnic differences in certain diseases, including inflammatory processes. The antagonist of cytokine IL-1, IL-1Ra, has been widely studied among Caucasian and African populations for genetic polymorphisms, and interethnic differences have been documented.However, the variation and genotype distribution of polymorphisms from these genes among South American Amerindians are thus far unknown. We present the results for a VNTR located in the IL-1Ra second intron, in a sample of 169 individuals belonging to 5 Native American populations from Argentina and Paraguay, identified as native according to their self designation, and their geographic location. We also compare this data with the results obtained from a sample of non-native Argentinian people. (Párrafo extraído a modo de resumen) - Artículo
Acceso Abierto Brain circuits mediating the orexigenic action of peripheral ghrelin: narrow gates for a vast kingdom(2015) Cabral, Agustina; De Francesco, Pablo; Perelló, MarioThe nervous and endocrine systems act together to regulate all physiological processes essential for the body homeostasis control. Given the strict communication restrictions that the brain–blood barrier (BBB) imposes, the interplay between these two systems requires a variety of delicate anatomical interfaces and physiological mechanisms that guarantee the precise function of the neuroendocrine system as a whole. The study of the mechanisms by which hormones act in the brain in order to regulate specific neuronal populations is a research topic rather neglected. Our group studies the neuronal circuitries and molecular mechanisms by which the stomach-produced hormone ghrelin regulates appetite and other physiological functions. A clear notion of the brain targets of peripheral ghrelin is essential for the comprehensive understanding of the physiological role of this hormone. Ghrelin is called “the hunger hormone” since it is the only known orexigenic peptide hormone. The target for ghrelin orexigenic actions is the brain, which contains a variety of ghrelin-responsive nuclei; however, several evidences suggest that the accessibility of peripheral ghrelin to the brain is strikingly low. Here, we briefly summarize the current knowledge in this topic and discuss this intriguing neuroendocrinological issue. - Artículo
Embargado First evidence of chromosomal variation within Chelonoidis chilensis (Testudines: Testudinidae)(2015) Sánchez, J.; Alcalde, L.; Bolzan, Agustín EduardoChelonoidis chilensis is an endangered tortoise that inhabits arid regions in Argentina, Bolivia and Paraguay. Blood samples were obtained from wild specimens from the Argentinan distribution range together with samples from specimens of known morphotype but unknown provenance. Cytogenetic analysis using Giemsa staining showed that the diploid chromosome complement was 2n=52 for all twenty-five tortoises analysed. Two different karyomorphs, termed A and B, were identified, with a karyotypic formulae of 7:5:14 and 6:5:15, respectively. G-band analysis suggests that karyomorph B may originate from a chromosomal fission event involving chromosome pair 7 of karyomorph A. In addition, all specimens analysed using Fluorescence In Situ Hybridisation (FISH) with a telomeric probe showed telomeric signals only at the terminal regions of chromosomes. This evidence suggests that the karyotype of C. chilensis does not have telocentric chromosomes, and that interstitial telomeric sequences have not played a major role during the recent chromosomal evolution of this species. Our data agree with recent molecular evidence supporting the existence of one instead several species for the C. chilensis complex. Our data further suggest a possible correlation between chromosomal variation and geographical distribution: karyomorph A is present in tortoises from the Dry Chaco Eco-region, whereas karyomorph B characterises tortoises living in the Monte of Steps and Plains Eco-region. Morphology appears to vary independently of cytomorph variation. - Artículo
Acceso Abierto The mitochondrial DNA history of a former native American village in northern Uruguay(2015) Sans, M.; Mones, P.; Figueiro, G.; Barreto, I.; Motti, Josefina; Coble, M.; Bravi, Claudio M.; Hidalgo, P.Objectives In 1828, between 8,000 and 15,000 Indians from the Jesuit Missions were brought to Uruguay. There, they were settled in a village, presently named Bella Unión, in the northwest corner of the country. According to historic sources, the Indians abandoned the settlement shortly thereafter, with the village subsequently repopulated by “criollos” and immigrants from abroad. As a first approach to reconstruct the genetic history of the population, data about the living population genetic structure will be used. Based on the analysis of the maternal lineages of the inhabitants of Bella Unión, and of those from two nearby villages, we expect to partially answer what happened with the first and subsequent inhabitants. Methods We analyzed the maternal lineages of the present inhabitants of Bella Unión and neighboring localities through the sequencing of the mitochondrial DNA control region. Results A total of 64.3%, 5.7%, and 30% of the mtDNAs were of Native, African, and West Eurasian origin, respectively. These figures are quite similar to that of the population of Tacuarembó, which is located in northeastern Uruguay. The four main Native American founding haplogroups were detected, with B2 being the most frequent, while some rare subhaplogroups (B2h, C1b2, D1f1) were also found. When compared with other Native American sequences, near- matches most consistently pointed to an Amazonian Indian origin which, when considered with historical evidence, suggested a probable Guaraní-Missionary-related origin. Conclusions The data support the existence of a relationship between the historic and present inhabitants of the extreme northwest Uruguay, with a strong contribution of Native Americans to the mitochondrial DNA diversity observed there. Am. J. Hum. Biol. 27:407–416, 2015. © 2014 Wiley Periodicals, Inc. - Artículo
Acceso Abierto Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons(Rockefeller University Press, 2015) López Soto, Eduardo Javier; Agosti, Francina; Cabral, Agustina; Mustafa, Emilio Román; Martínez Damonte, Valentina; Gandini, María Alejandra; Rodriguez, Silvia Susana; Castrogiovanni, Daniel; Felix, Ricardo; Perelló, Mario; Raingo, JesicaThe growth hormone secretagogue receptor type 1a (GHSR1a) has the highest constitutive activity of any G protein coupled receptor (GPCR). GHSR1a mediates the action of the hormone ghrelin and, its activation increases transcriptional and electrical activity in hypothalamic neurons. It is known that GHSR1a is present at some specific GABAergic presynaptic terminals; however, its impact on neurotransmitter release remains elusive. The voltage gated calcium channels, CaV2.1 and CaV2.2, control neurotransmitter release at presynaptic terminals and their activities are modulated by many GPCRs. Here we show that constitutive as well as agonist-dependent GHSR1a activation trigger a strong impairment of both CaV2.1 and CaV2.2 currents in rat and mouse neurons and in a heterologous expression system. Constitutive GHSR1a activity reduces CaV2 currents by a Gi/o-dependent mechanism that involves persistent reduction in channel density at plasma membrane, whereas, ghrelin-dependent GHSR1a inhibition is reversible and involves altered CaV2 current gating via a Gq-dependent pathway. Thus, we show that GHSR1a differentially inhibits CaV2 channels by Gi/o- or Gq-protein pathways depending on its activation mode. Moreover, we present evidence suggesting that GHSR1a-mediated inhibition of CaV2 impairs GABA release in hypothalamic neurons, a mechanism that could contribute to neuronal activation by the disinhibition of postsynaptic neurons. - Artículo
Acceso Abierto Asociación entre polimorfismos del gen NAT2 y fisura labiopalatina no sindrómica en Argentina(2015) Santos, María Rita; Ramallo, Virginia; Muzzio, Marina; López Camelo, Jorge Santiago; Bailliet, GracielaBackground: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment. Aim: To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP. Material and methods: We analyzed *5 (481C>T), *6 (590G>A) and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT). Results: TDT showed a positive association between allele *5 and NSCLP (odds ratio=1.6; p=0.03). Conclusions: The presence of *5 allele is significantly higher in cases with congenital NSCLP.
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